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Exogenous IL-7 induces Fas-mediated human neuronal apoptosis: potential effects during human immunodeficiency virus type 1 infection.
- Source :
-
Journal of NeuroVirology . Aug2005, Vol. 11 Issue 4, p319-328. 10p. - Publication Year :
- 2005
-
Abstract
- The use of exogenous cytokines is part of translational immune-antiretroviral approaches to induce immune reconstitution and possibly eliminate the persistence of human immunodeficiency virus type 1 (HIV-1) in virally suppressed infected individuals on highly active antiretroviral therapy (HAART). Recently, our laboratories demonstrated that interleukin-7 (IL-7) has significant efficiency in stimulating HIV-1 replication from proviral latency in CD4+ T lymphocytes of infected patients. The authors now investigated the possible role of IL-7 in HIV-1–associated dementia (HAD). The authors demonstrated that the IL-7 receptor is expressed on both human neurons (i.e., differentiated NT2 cells) and human astrocytes, with relatively higher mRNA levels in neurons. The translational protein levels of IL-7 receptor α were not proportional to those of the mRNA levels in these central nervous system (CNS)-based cell types. Exogenous IL-7 was observed to only slightly down-regulate IL-7 receptor α expression on both neurons and astrocytes, as assayed by Western blotting. Instead of promoting survival, surprisingly, exogenous IL-7 induced neuronal apoptosis, as detected by TUNEL assays. Furthermore, IL-7 augmented neuronal apoptosis induced by HIV-1 gp120. Human apoptosis genomic microarray analyses of IL-7–treated human neurons showed up-regulated expression of proapoptotic genes: protein kinases, caspase-10, FAST kinase, tumor necrosis factor (TNF) receptor, and BCL2-antagonist of cell death. These data suggest that IL-7 leads to neuronal apoptosis by a molecular mechanism(s) that occurs via Fas-mediated activation-induced cell death. These studies may therefore not only be key in evaluating the potential use of IL-7 in vivo as a therapeutic modality, but also suggest that IL-7, which is increased endogenously in HIV-1–infected individuals late in disease, may be involved in the neuronal apoptosis demonstrated during HAD. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HIV
*APOPTOSIS
*HIV infections
*CYTOKINES
*PHOSPHOTRANSFERASES
*NERVOUS system
Subjects
Details
- Language :
- English
- ISSN :
- 13550284
- Volume :
- 11
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of NeuroVirology
- Publication Type :
- Academic Journal
- Accession number :
- 18289232
- Full Text :
- https://doi.org/10.1080/13550280500187005